DEXAMETHASONE ENHANCES THE OSTEOGENIC EFFECTS OF FLUORIDE IN HUMAN TE85 OSTEOSARCOMA CELLS IN-VITRO

The in vitro osteogenic effects of fluoride have not always been consi stently observed in human bone cells. The present study sought to test if dexamethasone (Dex) could potentiate the action of fluoride to inc rease the detectability of the stimulatory effects of fluoride on [H-3 ]thymidine incorporation, alkaline phosphatase (ALP) specific activity , collagen synthesis, and osteocalcin secretion in human TE85 osteosar coma cells. Neither Dex at 10(-10)-10(-6) M or fluoride at a mitogenic dose (100 mu M) had any consistent stimulatory effects on thymidine i ncorporation. When the cells were treated with both agents simultaneou sly, significant and highly reproducible stimulations were observed. T he mitogenic effects of the two agents were confirmed with cell number counting. Analysis of variance (ANOVA) revealed a significant interac tion (P < 0.001) between fluoride and Dex on cell proliferation. The e nhancing effect of Dex on [H-3]thymidine incorporation was not due to a shift of the optimal dose response of fluoride. Though fluoride alon e or Dex alone also had no consistent effect on ALP specific activity, the co-treatment with fluoride and Dex for 24 hours produced signific ant (P < 0.001, ANOVA) stimulation in ALP specific activity. Fluoride alone had no consistent effect on collagen synthesis and on 1,25(OH)(2 )D-3-dependent osteocalcin secretion, whereas Dex treatment consistent ly inhibited these two osteoblastic parameters in a dose-dependent man ner. However, both the collagen synthesis and osteocalcin secretion ra tes were significantly higher (P < 0.001 ANOVA for each) when the cell s were co-treated with Dex and fluoride (100 mu M) than when they were treated with Dex alone. Thus, these data indicate that the response i n collagen synthesis and osteocalcin secretion to fluoride stimulation was more readily observed in the presence of Dex than in its absence. ANOVA analysis revealed that the interaction between fluoride and Dex on collagen synthesis, but not the 1,25(OH)(2)D-3-dependent osteocalc in secretion, was significant (P < 0.02). In summary, we have demonstr ated for the first time that in TE85 cells (1) Dex potentiated the eff ects of fluoride on cell proliferation, ALP specific activity, and col lagen synthesis; (2) while Dex at 10(-7)-10(-6) M alone inhibited the collagen synthesis and at 10(-9)-10(-6) M reduced osteocalcin secretio n, Dex at 10(-8)-10(-6) M significantly stimulated the proliferation o f TE85 cells; and (3) Dex interacted with fluoride to increase the per centage of experiments showing an osteogenic action of fluoride. In co nclusion, the in vitro osteogenic actions of fluoride in human TE85 ce lls are more consistently observed in the presence than in the absence of Dex.